Role of TGF-beta in immune-evasion of cancer.

One of the major obstacles in tumor-immunology is the outgrowth of malignant tumors despite their immunogenicity and recognition by the immune-system. Multiple mechanisms for this phenomenon have been proposed. We review the possible involvement of transforming growth factor beta (TGF-beta) in this context. TGF-beta is a cytokine with pleiotropic functions, involved in multiple physiologic processes including immunoregulation. Immune elimination of most cancers ultimately depends on cytolytic T cells (CTL). We propose a mechanism of specific suppression of cytolytic T cell (CTL)-responses mediated through immunoglobulin-bound TGF-beta (IgG-TGF-beta), secreted by activated B cells, and a cell of myeloid origin. This mononuclear "Veto" cell presumably binds IgG-TGF-beta through Fc-receptors and activates latent TGF-beta. The suggestion that B cell responses can inhibit tumor rejection is supported by observations in B cell-deficient mice. Ways for enhancing effective cancer immunity by interfering with the network of interactions involving IgG-TGF-beta are discussed. Copyright 2001 Wiley-Liss, Inc.